FIELD OF THE INVENTION
The present invention relates to new families of mammalian, notably human and rat, acidity-sensitive ionic channels. More particularly, the invention relates to the identification and molecular characterization in humans and rats of a new family of proton-activated cationic channels, collectively referred to below as ASIC polypeptides, for Acid Sensing Ionic Channel.
The ASIC channels constitute the first members of a group of cationic channels belonging to the family of amiloride-sensitive degenerine sodium channels [6, 11-14], which are activated temporarily by extracellular acidification.
Sensitivity to acid is associated with both nociception [1] and the transduction of taste [2]. The stimulation of sensory neurons by acids is of great importance because acidity accompanies numerous painful inflammatory and ischemic situations. The pain caused by acids is thought to be mediated by the cationic channels present at the level of the sensory neurons which are activated by protons [3-5]. The biophysical and pharmacological properties of the ASIC channels of the invention are similar to those of the proton-activated cationic channels described in the sensory neurons [3, 15, 16]. However, as will be seen in the description below, to date there has been no report of ligand-activated ionic channels simpler than the ASIC channels.